This application is a continuation-in-part of Ser. No. 103,779 filed Oct. 2, 1987, which is in turn a continuation-in-part of Ser. No. 786,765 filed Oct. 11, 1985, now abandoned, which is in turn a continuation-in-part of Ser. No. 664,901 filed Oct. 26, 1984, now issued as U.S. Pat. No. 4,547,538 which is in turn a continuation-in-part application of Ser. No. 350,536 filed Feb. 2, 1982 now issued as U.S. Pat. No. 4,480,092.
This invention relates to novel monoprimary-disecondary triamines and a method for their preparation from polyalkylene polyamines ("PAPA" for brevity). Such monoprimary-disecondary amines are useful as stabilizers for organic polymers, for use as curing agents for epoxy resins, and as starting materials for the preparation of polysubstituted piperazinones disclosed in the related prior case U.S. Pat. No. 4,547,538 issued Oct. 11, 1985, the disclosure of which is incorporated by reference thereto as if fully set forth herein.
Though it would seem that alkylation of a PAPA should be relatively straightforward, the reaction between alkyl halides and primary amines is not usually a feasible method for the preparation of an expected alkylated product amine, because the reaction does not stop after alkylation of the primary amine group, even if this is the only amine group in the amine reactant. Secondary amines are stronger bases than the amine reactant substrate, and therefore the secondary amine group preferentially attacks the alkyl halide yielding a tertiary amine. Therefore when both primary and secondary amine groups are present in the amine to be alkylated, a wide assortment of alkylated products is formed even under the most controlled conditions (see "Advanced Organic Chemistry Reactions, Mechanisms and Structures" by J. March, 3d edition, btm of pg. 365 John Wiley & Sons 1984.) For this reason, generally, alkylation with an alkyl halide is used where a tertiary amine is desired and one expects to effect complete alkylation of all amine groups. Even carefully controlled conditions generally give a mixture of alkylated products and is not favored even on a laboratory scale.
Alkylation of PAPA has been of considerable interest in the past and methods have been reported by Agnew, N. H. in Journal Chemical Society (London) Sec. C pg 203-208 (1966), and in U.S. Pat. No. 3,051,751. A process for selectively alkylating the secondary amino groups in a PAPA was disclosed in U.S. Pat. No. 3,565,941 and monotertiary-diprimary triamines are disclosed in U.S. Pat. No. 3,280,074.
A process is disclosed in U.S. Pat. No. 3,151,160 to Spivack for the preparation of tertiary-amino-alkylated primary amines in which the bridge nitrogen is tertiary. As Spivack states, even in this alkylation reaction where a very large excess of the reactant amine is used, this method is limited to only the simpler diamines because the inherent non-selective nature of the reaction leads to more or less random substitution of other replaceable hydrogens which results in drastic reduction in yields in the case of somewhat complex reactant amines. Spivack reiterates what has always been the problem with respect to the preparation of amines represented by structures which, on paper, look quite obvious. It is not obvious how one can go about obtaining an essentially pure amine by any type of alkylation reaction, even reductive alkylation.
By "essentially pure" I refer to an amine product of specified structure which is at least 90% pure.
The preparation of diprimary triamines having a secondary or tertiary N atom intermediate primary end groups is disclosed in U.S. Pat. No. 4,293,682. Because each of the C atoms adjacent the primary amine end groups (referred to as "N-adjacent C atom") is disubstituted, the primary amine end groups are hindered and such diprimary PAPA are not susceptible to the selective alkylation process of this invention in which the alkylated product is to have only one primary end group alkylated. Where a PAPA triamine has only one hindered primary amine end group, the other end group being unhindered, one might expect that only the unhindered amine group would be alkylated under conventional alkylation conditions, but both amine end groups are often alkylated, and maybe also the secondary amine.
U.S. Pat. No. 2,393,825 to Senkus teaches that a nitroamine may be prepared by reacting a primary or secondary amine with formaldehyde to form the corresponding N-hydroxymethyl, mono-, or dialkylamine, which is in turn reacted with an equimolar quantity of a secondary nitro-paraffin to produce the desired nitroamine. This series of reactions may be illustrated as follows: EQU R.sup.1 NH.sub.2 +HCHO.fwdarw.R.sup.1 NHCH.sub.2 OH
the addition occurring at the terminal amine group, whether primary or secondary. If there were two amine groups, the addition reaction would be expected to occur at each amine group, though not to the same extent, particularly if one amine group was primary and the other was secondary.
Thereafter, the N-hydroxyalkylamine is reacted with a secondary nitroalkane, thus: ##STR1## In an analogous manner, one may start with a secondary amine R.sup.1 --NH--R.sup.2 and HCHO to produce ##STR2## After hydrogenation of the nitroamine, the general formula of the polyamines which are made by the Senkus procedure is represented as follows: ##STR3## wherein R may be H, alkyl, or hydroxyalkyl; R.sup.1 may be alkyl or hydroxyalkyl; and, R.sup.2 and R.sup.3 are alkyl.
In each case, the nitro group may be hydrogenated if the nitro group is on the tertiary C atom of a primary or secondary amine. But in Senkus' reduced compound (with the primary amine group), R.sup.1 and R.sup.2 cannot both be H.
If the starting material is a diamine, rather than a primary or a secondary monoamine, and one tried to form a product with only one N-hydroxymethylamine group, one might use only a single mole of HCHO with the expectation that only one of the amine groups in the starting diamine would be hydroxymethylated. It would then be possible with this modification of the teaching of Senkus, to produce a compound which is similar to the precursor of our claimed PAPA.
Pursuing this modification of Senkus one would react nitropropane, formaldehyde and ethylenediamine as follows: ##STR4## This nitroamine would then be hydrogenated to yield ##STR5## Because it is essential that the unhindered primary amine group be substituted, one would expect that the polyamine could be alkylated as suggested by Kyrides in U.S. Pat. Nos. 2,267,204 and 2,267,205.
The Kyrides polyamine is represented as follows: EQU X--NH--R--(NH--R).sub.n --NH--Y
which is formed by an alkylation reaction with a primary alkyl group, to introduce a long chain alkyl group in the structure. He defines: X is H or alkyl, R is an alkylene radical, and Y is alkyl. He states that both X and Y may preferably be the normal (straight chain) alkyl groups; however, forked or branched chain alkyl groups may be employed. (see '204, col 1, lines 43-46).
For our comparison purposes, X must be H. In the '204 and '205 patents, Y is a predominantly straight chain primary alkyl group, though he states (in '204) it may be branched. By "branched" he refers to a primary alkyl group derived from a primary alkyl halide, and not to a secondary alkyl group. In his example, 2-ethylhexyl is branched, but note that it is a primary alkyl group. The reason for his use of primary alkyl groups is because the secondary alkyl groups will not alkylate the amine in his method. The reaction does not proceed because of the steric hindrance at the halogen-bearing carbon atom.
We attempted to alkylate a large excess of the diamine, N-(2-amino-2methylpropyl)-1,2-ethanediamine, obtained by hydrogenating the compound N-(2-methyl-2-nitropropyl)-1,2-ethanediamine having the structure: ##STR6## (made as described in our U.S. Pat. No. 4,698,446) with 1-chlorocyclohexane. There was no trace of the alkylated product in the reaction mass.
The difficulty of alkylating an amine with a secondary alkyl group is well known. For example, in Great Britain 2,070,011 to Jachimowicz, piperazine is alkylated with cyclohexene in the presence of a rhodium organometal catalyst and carbon monoxide, to obtain 1,4-dicylcohexyl-methyl-piperazine as follows: ##STR7## In the alkylated product, the resulting linkage is through CH.sub.2, which is a primary linkage derived from the CO. Therefore this alkylation procedure would not result in our claimed compound.
Thus, the difficulty of obtaining any N-(2-propyl)-N'-(2-amino-2methylpropyl)-1,2diaminoethane, let alone essentially pure product, is evident. It will also be clear to those skilled in the art that unless the PAPA is essentially pure, its use for any practical application, is constricted.
The direct alkylation of a primary amine used in Kyrides '204 is the result of an N-alkylation reaction with a primary alkyl group. This reaction does not proceed with a secondary alkyl group as explained hereinabove. For example, our efforts to alkylate our precursor compound with 1-chlorocyclohexane does not result in the N-cyclohexylated product but with the formation of cyclohexene.
Thus, if one were to make a triamine with a Senkus starting material modified to include an alkyleneimine linkage, one would end up with a triamine with terminal primary amine groups one being hindered, and the other unable to be alkylated with a secondary alkyl group.
It appears that the '204 compounds can be readily modified. The isopropyl linkage between two amine groups in the '204 compound would appear to be readily substituted with an isobutyl linkage. However, it is essential that the methine C atom in the isopropyl linkage be substituted or it would not be the claimed compound, for example: ##STR8## while the Kyrides compound would be written ##STR9## Specifically, in the N-2-ethylhexyl ethylene diamine (pg 2, line 46 in '204) the alkyl group is a primary alkyl group, while N-1-ethylhexyl is a secondary alkyl group.
If one was to alkylate to introduce the secondary alkyl group, with a rhodium organometal catlayst and CO, the CO will generate a CH.sub.2 linking group making the alkyl group a primary one. To obtain the claimed compound, the alkyl group must be secondary.
It is important to note that each of the foregoing Kyrides references eschews making any suggestion that an essentially pure PAPA is produced, and of course, for use as insecticides or detergents, they need not be. One would also expect that the known catalytic alkylation with an olefin, such as is disclosed in Jachimowicz would provide a mixture of PAPA, not an essentially pure one.
Since both the hydrohalo elimination and alkylation reactions proceed concurrently, it is essential that the latter proceed preferentially if a reasonably pure, useful amine product is to be synthesized.
An appreciation of the magnitude of the difference between alkylation with a primary alkyl halide and a secondary alkyl halide may be derived from an examination of the rate constants for the substitution of alkyl bromides in 80% ethanol at 55.degree. C. The second-order rate constant (because the reaction is predominantly second order) for isopropyl bromide is about 30 times slower than for ethyl bromide (see the textbook Structure and Mechanism in Organic Chemistry by C. K. Ingold, Table 24-1, pg 318, Cornell University Press).
The elimination reaction (bimolecular olefin formation from alkyl bromides) in ethyl alcohol at 25.degree. C. has a rate constant of 11800 for isopropyl bromide, but only 2500 for ethyl bromide; this shows that elimination with a secondary halide is more than 4.5 times faster (see Ingold, supra, Table 31-7, pg 437).
In particular, we find that if the reaction of 1-chloro-2-methyl-2-aminopropane with N-(2-propyl)-1,2-diaminoethane yields any N-(2-propyl)-N'-(2-amino-2-methyl-propyl)-1,2-diaminoethane at all, it is formed in so small an amount that it would not be feasible to separate it from its isomer N'-(2-amino-2-methylpropyl)-N'(2-propyl)-1,2-diaminoethane, which is also formed, not to mention the many other alkylated products which are predominantly formed.
The reductive alkylation of PAPA is well known and described with numerous examples in the chapter entitled "Preparation of Amines by Reductive Alkylation" by W. S. Emerson in Organic Reactions, Vol 4, John Wiley & Sons, New York, N.Y. Examples are given for preparation (A) of tertiary amines from (i) secondary aliphatic amines and ketones, (ii) aryl alkyl amines and aliphatic aldehydes, (iii) aryl alkyl amines and ketones; etc., and, (B) of secondary amines by (i) reduction of Schiff's bases derived from aliphatic amines, and from aromatic amines, and (ii) reduction of primary aromatic amines, nitro or nitroso so compounds and ketones. etc. In reductive alkylations with an aldehyde there is a wide scatter of side reaction because of the higher reactivity of an aldehyde than a ketone. There is no teaching that reductive alkylation with a ketone may result in alkylation only at a particular amino group substantially to the exclusion of all other amino groups, such result being obtained with a PAPA only by hindering one of the two primary amine groups and reacting with a ketone.